We showed that spironolactone reduced structural damage and prevented renal dysfunction in chronic cyclosporine (CsA) nephrotoxicity. These findings evidenced an aldosterone renal vascular effect under this condition. To investigate aldosterone role in modulating renal vascular tone, renocortical vasoactive pathways mRNA-levels in chronic CsA-nephrotoxicity as well as spironolactone effect on renal function in acute CsA-nephrotoxicity were evaluated. Two experiment sets were designed. For chronicnephrotoxicity, rats fed with low-sodium diet were divided in groups receiving vehicle, spironolactone (Sp), CsA, and CsA+Sp, during 21-days. Creatinine clearance, survival percentage and renocortical mRNA-levels of pro-renin, angiotensinogen (Ang), angiotensin receptors (AT_1A, AT_1B and AT₂), preproendothelin, endothelin receptors (ET_A, ET_B), cyclooxygenase-2 (COX-2), and adenosine receptors (Ad₁, Ad_2A, Ad_2B and Ad₃) were analyzed. For acute-nephrotoxicity, similar groups fed with standard chow diet during 7-days were included. Serum potassium and sodium, glomerular filtration rate (GFR), and renal blood flow (RBF) were determined. In chronic model, CsA produced pro-renin and ET up-regulation, altered adenosine receptors expression and reduced Ang, AT_1A, AT_1B, ET_B, and COX-2 mRNA levels. Spironolactone protective effect in chronic-nephrotoxicity was associated with prevention of pro-renin up-regulation and increased AT₂, together with ET_B reduction. In acute-nephrotoxicity, spironolactone completely prevented GFR and RBF reduction induced by CsA. Our results suggest that aldosterone contributes to renal vasoconstriction observed in CsA-nephrotoxicity and renoprotection conferred by spironolactone was related with modification of renocortical vasoactive pathways expression, in which pro-renin normalization was the most evident change in chronic-nephropathy. Finally, our data pointed out to spironolactone as a potential treatment to reduce CsA-nephrotoxicity in transplant patients.